Publications by authors named "Sophia G Moesgaard"

Species selection plays a pivotal part during non-clinical safety assessment in drug development. If possible, use of non-human primates (NHPs) should be avoided due to ethical considerations. However, limiting factors as lack of pharmacologic activity in other species could necessitate use of NHPs.

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An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within regulatory general toxicology studies. Anonymised data on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides and 6 antibody-drug conjugates) were submitted by 18 organisations. The use of one or two species across molecule types, the frequency for reduction to a single species within the package of general toxicology studies, and a comparison of target organ toxicities identified in each species in both short and longer-term studies were determined.

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Few methods for noninvasive assessment of arterial stiffness and endothelial dysfunction in porcine models are available. The aim of this study was to evaluate methods for assessment of arterial stiffness and endothelial dysfunction in anesthetized Göttingen minipigs. Pulse-wave velocity (PWV) was assessed in male Göttingen minipigs (n = 8; age approximately 60 wk) by using applanation tonometry of the carotid and femoral arteries.

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An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk.

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The Göttingen minipig model of obesity is used in pre-clinical research to predict clinical outcome of new treatments for metabolic diseases. However, treatment effects often remain unnoticed when using single parameter statistical comparisons due to the small numbers of animals giving rise to large variation and insufficient statistical power. The purpose of this study was to perform a correlation matrix analysis of multiple multi-scale parameters describing co-segregation of traits in order to identify differences between lean and obese minipigs.

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Objectives: We aimed to develop a porcine model for chronic nonischemic mitral regurgitation (MR) to investigate left ventricular (LV) enlargement and eccentric hypertrophy.

Design: Nonischemic MR was induced in 30 pigs by open-chest immobilization of the posterior mitral leaflet by transannular traction sutures that where applied in transmyocardial fashion. A sham operated control group (n = 13) was included.

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Objective: NON-ISCHEMIC MITRAL REGURGITATION (MR) IS PRIMARILY CAUSED BY MYXOMATOUS MITRAL VALVE (MV) DISEASE LEADING TO ADAPTIVE REMODELING, ENLARGEMENT, AND DYSFUNCTION OF THE LEFT VENTRICLE. THE AIM OF THIS STUDY WAS TO EXAMINE THE REGULATION OF PLASMA MARKERS AND SEVERAL CARDIAC KEY GENES IN A NOVEL PORCINE MODEL OF NON-ISCHEMIC MR.

Methods And Results: Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls.

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Background: Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.

Methods And Findings: The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria.

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The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs.

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Cytokines have been associated with the progression of congestive heart failure (CHF) in humans and may be implicated in the pathophysiology of myxomatous mitral valve disease (MMVD) in dogs. The aim of this study was to determine the serum concentrations of cytokines in dogs with MMVD. The study included 16 Cairn terriers with no or minimal mitral regurgitation (MR), 41 Cavalier King Charles Spaniels (CKCS) with different degrees of MR and 11 dogs of different breeds with CHF due to MMVD.

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Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the L-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability.

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Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs.

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Background And Aim Of The Study: Little is known of the local role of nitric oxide (NO) in heart valves in relation to heart valve diseases. The study aim was to examine NO release and the expression of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in relation to early local changes in porcine mitral valves.

Methods: A histological evaluation of mitral valve leaflets from slaughter pigs and sows was made, and the expression of eNOS and iNOS protein measured using immunohistochemistry.

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The aim of the study was to compare the effect of 2 angiotensin-converting enzyme (ACE) inhibitors on neurohormonal and circulatory variables in Cavalier King Charles Spaniels (CKCSs) with asymptomatic mitral regurgitation (MR). Ten CKCSs with mild to severe untreated MR were treated with 2 ACE inhibitors, quinapril and enalapril (each at 0.5 mg/kg PO q24h for 7 days), in a double-blind, crossover study with a washout period of 7 days between treatments.

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Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves (desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.

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Ghrelin is a peptide identified as an endogenous ligand for the growth hormone secretagogue receptor. Studies have shown that ghrelin stimulates growth hormone, promotes food intake and decreases energy expenditure. Furthermore, feeding status seems to influence plasma ghrelin levels, as these are increased during fasting, whereas feeding and oral glucose intake reduce plasma ghrelin.

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